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Objectives The aim of the study was to compare the quality of sedation with 3 different sedation regimens in upper gastrointestinal endoscopy (UGIE) in pediatric patients. Methods One hundred fifty consecutive children who underwent UGIE were randomly assigned to 1 of the 3 medication regimens. Patients in group A (n = 49) received placebo. Forty-five minutes after the placebo was given, repeated intravenous (IV) doses of 0.1 mg/kg midazolam were administered titrated to achieve a level of deep sedation. Patients in group B (n = 51) received oral ketamine instead of placebo, and patients in group C (n = 50) received oral fentanyl instead of placebo with the same methodology and sedation endpoint. Results The mean dose of midazolam administered in group B patients was remarkably lower compared with that of groups A and C. Patients in group B showed less distress in IV line placement and separation from parents, higher comfort level, more endoscopist satisfaction, and higher sedation depth compared with groups A and C. The recovery time was significantly shorter in group B. All of the 3 regimens were safe. All of the complications were managed successfully. Conclusions Our data suggest that synergistic sedation with oral ketamine and IV midazolam for UGIE in children is a suitable and safe sedation. The higher rate of vomiting in group B in contrast to previous studies must be caused mainly by the oral route of ketamine administration.

Background: Nowadays, there is an increasing interest in noninvasive methods to diagnose Helicobacter pylori infection. Indeed, they can profitably replace endoscopy in predicting the diagnosis. The stool antigen test for H. pylori is a noninvasive immunoassay to diagnose active infection with this bacterium in human fecal samples. The aim of this study was detection of alkyl hydroperoxide reductase protein (AhpC) antigen by immunoblotting in stool samples for diagnosis of H. pylori. Materials and Methods: Chromosomal DNA from H. pylori was isolated. AhpC gene was amplified by PCR, These amplicons were cloned into pTZ57R ⁄ T cloning vector then subcloned into pQE30 expression vector and overexpressed using isopropyl-beta-D-thiogalactopyranoside in E. coli M15. AhpC protein was purified by affinity chromatography. Rabbits were immunized with the purified AhpC protein for the production of antibodies. To determine the accuracy of the test for diagnosing H. pylori infection from stool, we evaluated 84 patients (6–81 years old) using Western blot analysis by rabbit anti-AhpC antibody. Positive rapid urease test on biopsy samples was considered as the gold standard. Results: AhpC gene was overexpressed, and AhpC protein was purified. Rabbit anti-AhpC antibody produced after immunization with the purified AhpC protein. By immunoblotting, we detected AhpC protein in the positive stool samples. The test showed a 83.3% sensitivity (95% CI: 69.8–92.5%) and a 91.7% specificity (95% CI: 77.5–98.2). Among the children, the sensitivity was 88.2% (95% CI: 63.6–98.5) and the specificity was 100% (95% CI: 69.2–100); in adults, the sensitivity and specificity were 80.6% (95% CI: 62.5–92.5) and 88.5% (95% CI: 69.8–97.6), respectively. Conclusions: Using of AhpC antigen for diagnosis of H. pylori infection is a useful noninvasive method, accurate in adolescents and children, and can be used for the development of a stool antigen detection kit for H. pylori. Helicobacter ISSN 1523-5378

Objective: To study the clinical presentation, histology and colonoscopic features of lower gastrointestinal polyps in Iranian children. Material and Methods: Medical reports of children with colorectal polyps were retrospectively reviewed from 1996 to 2005 at the Children’s Medical Center Hospital, Iran. A total of 563 cases were studied. Data related to age, sex, family history, signs and symptoms, the size, location, polyp types and associated lesions were collected and analyzed. Results: The mean age of children was 5.66 ± 2.88 years (range 2 months to 17 years), with a male-to-female ratio of 1.61:1.0. The highest incidence was between ages 2 and 10 years (85.1%). Rectal bleeding was the presenting symptom in 78.5% cases. The polyps were solitary in 94% of cases. A majority of polyps (86.3%) were juvenile and 86.7% located in the rectosigmoid area. Three percent of cases had a positive family history. One case of Turcot syndrome was also identified. Conclusion: Juvenile polyps remain the most common polyps in Iranian children. Although the presence of a solitary polyp in the rectosigmoid colon is more prevalent, in a significant number of cases they are multiple and located in proximal parts. Polyps must be removed even when asymptomatic because of their probable neoplastic potential.

Background/Aims: There is little data concerning the incidence of alpha-1-antitrypsin”(AAT) deficiency, the most common genetic cause of liver disease, among children with neonatal cholestasis in Iran. Thus, this study was performed to analyze AAT deficiency in this group of patients. Materials and Methods: DNA samples from patients with neonatal cholestasis were investigated for Pi S and Pi Z alleles, using polymerase chain reaction–restriction fragment length polymorphism. Results: Thirty patients with neonatal cholestasis were enrolled. Among those who underwent biopsies, the results revealed neonatal hepatitis in 19, bile duct paucity in 1, steatohepatitis in 1, bile duct proliferation in 1, cirrhosis in 2, fibrosis in 2, and extrahepatic biliary atresia in 1 patient. No mutant allele was found in any patient. Conclusion: The incidence of AAT deficiency is very low in Iran; therefore, screening for AAT is not recommended for patients with neonatal cholestasis in Iran.

Dear Editor, Cystic Fibrosis (CF), characterized by abnormal transport of chloride and sodium ion across the epithelium, leads to thick, viscous secretions (1). The hallmark signs and symptoms of cystic fibrosis are salty tasting skin, poor growth and poor weight gain despite a normal food intake, accumulation of thick, sticky mucus, frequent chest infections, and coughing or shortness of breath. Males can be infertile due to congenital obstruction of vas deferens. Symptoms often appear in infancy and childhood, such as bowel obstruction due to meconium ileus in newborn babies (2, 3). Cystic fibrosis may be diagnosed by many different methods including newborn screening, sweat testing, and genetic testing (4). The prognosis for cystic fibrosis has improved due to earlier diagnosis through screening, better treatment and access to health care (5). This disease is specified by very wide spectrum of clinical manifestations for which many differential diagnoses have to be considered. We studied 300 patients of CF in Children’s Medical Center in Tehran, during 2006 to 2012. Necessary information including age, sex, and symptoms of patients such as cough, hemoptysis, recurrent pulmonary infection, nasal polyposis, recurrent sinusitis, intestinal obstruction, intussusception, reflux, rectal prolapse, pancreatitis, fatty diarrhea, edema and hypo-albuminemia, anemia, vomiting and dehydration attack, cirrhosis, biliary atresia, portal hypertension, salty skin, failure to thrive (FTT), clubbing, coagulation disorder, bone fracture and nyctalopia was entered in the checklists. First manifestation of each patient was also noted. The main complaint of patients was isolated FTT and this complication had occurred in 74 (24.7%) patients. In addition, FTT with another complication was observed in 28 (9.3%) patients at the beginning of the disease; in other words, isolated failure to thrive or FTT associated with other symptoms of the disease was seen as first clinical presentation in about one-third of the patients (that is, 102 patients). The most common complication next to FTT was pulmonary infection which was seen in 47 (15.7%) patients. Other common first clinical presentations of cystic fibrosis include: attacks of vomiting and dehydration in 45 (15%), cough in 25 (8.3%), intestinal obstruction (meconium ileus) in 23 (7.7%), fatty diarrhea in 18 (6%), FTT with fatty diarrhea in 11 (3.7%), edema and Hypo-albombinemia in 10 (3.3%), and biliary atresia in 6 (2%) patients. Other symptoms including anemia, salty skin, coagulation disorders, gastro esophageal reflux, and sinusitis were seen in less than five patients. In 30 (10%) patients, two of the mentioned complications were observed simultaneously. At onset of disease, among a total of 300 patients, 182 (60.7%) had gastrointestinal symptoms, and 72 (24%) patients had respiratory tract symptoms. CF may be diagnosed after a long period of illness, by different symptoms and laboratory tests (6). In a similar study by Fallahi et al. in Iran, prevalence of first clinical presentations of CF patients before the diagnosis was as follow: gastro intestinal symptoms in 152 (62.6%), respiratory symptoms in 93 (38.3%), isolated FTT or in combination with other symptoms in 34.9%, diarrhea in 28.8%, vomiting in 15.6%, cough in 30% and respiratory distress in 23.9% patients (6). As mentioned before, the first complication in 7.7% of our patients was ileus meconium which is similar to results of other studies (4). According to this study, gastrointestinal symptoms were the most common symptoms associated with CF disease. In a study by McCloskey more than two thirds of patients presented with respiratory symptoms including chronic sino-pulmonary disease, nasal polyps or recurrent respiratory tract morbidity. This study tried to bring up the most common presenting symptoms of CF. With more attention to the symptoms of this disease, the diagnosis could be established earlier and upcoming complications prevented.

Iron deposition in liver is a major finding in thalassemic patients and because of direct iron toxicity to liver it is associated with several consequences for example liver fibrosis. Liver biopsies from 63 patients were evaluated, 40 (63.5%) were male and 20 (36.5%) were female. The mean age of the patients was 8.01 ± 3.7 and the age range was from 1.8 to 15 years. Histologic grading and staging was performed for each case according to modified HAI (Hepatitis Activity Index) system. Iron scoring was performed according to Sindram & Marx and MTK1-3 scoring systems. The mean (SD) dry weight (dw) of liver specimens was 1.34 (0.11) mg (range 0.20 to 3.80 mg). The mean (SD) of hepatic iron concentration was 230.9 (121.2)μmol/g dry weight. The relationship between the variables HIC, HII (hepatic iron index) and all histological gradings of iron (S&M and MTK1-3) was very strong. The relationship between the HIC and staging by HAI method was good. Significant differences were identified between the mean HIC in scores 1&2 of all histological iron scorings (S&M and MTK1-3), but no significant differences identified between mean HIC in other adjacent scores in all histological iron scorings (S&M and MTK1, 2 and 3). New scoring system introduced by us in this study which considered size and density of iron granules as well as zone of iron deposition was very much the same as simple Sindram and Marx classification.

Helicobacter pylori infection is acquired mainly in childhood, especially in developing countries, where a low-cost, rapid diagnostic technique which is reliable for all age groups may be useful for the management of H. pylori infection. For this purpose, we used an HpSA test (Equipar) to detect H. pylori infection in children and adolescents from Tehran, Iran. Thirty-five children who were positive or negative for H. pylori infection by endoscopy-based tests were used as positive and negative controls for the HpSA test. Stools were collected from 430 randomly selected children and adolescents (4 to 18 years old) from southwest, near the center, and northwest of Tehran. A questionnaire that included presence of recurrent abdominal pain (RAP), family history of infection and/or peptic ulcer disease (PUD), and income of parents was completed. A good agreement was found between the results of endoscopy-based tests and those of the HpSA test; the sensitivity and specificity of the Equipar-HpSA test were 100% and 83.4%, respectively. Among 430 children and adolescents, 47% were positive by the HpSA test, of whom 82% had RAP. No difference in incidence was observed between the two sexes; the various categories of age showed an increasing incidence, ranging from 24% (ages 4 to 6) to 58% (ages 16 to 18). The rate of infection in children and adolescents from the southwest was significantly higher (70%) than the rate in those from the northwest (32%), and a family history of H. pylori infection or PUD was observed in 59% of the HpSA positive subjects. The HpSA test is a useful test to detect H. pylori infection in children and adolescents from developing countries.

Dear Editor, Neonatal cholestasis (NC) is defined as prolonged elevation of serum levels of conjugated bilirubin beyond two weeks of life. The two most common causes of NC are biliary atresia (BA) and idiopathic neonatal hepatitis (INH). Early and accurate differentiation of these two entities is very important and determines the prognosis and curability of cholestasis. BA requires surgical intervention as soon as possible; whereas, INH needs medical management (1-3). There is no single non-invasive test that can definitely differentiate these two entities. The gold standard for the diagnosis of BA is intraoperative cholangiography. Liver biopsy is the investigation with high diagnostic usefulness in NC. Its diagnostic accuracy for NC has been more than 90% in several studies (1, 4-6). Alagille identified four clinical features that, although nonspecific, supported the correct diagnosis of intrahepatic or extrahepatic cholestasis in 82% of the cases. These clinical variables included stool color within 10 days of admission, age at onset of acholic stools, birth weight, and the features of hepatic involvement, specifically the presence of hepatomegaly and consistency of the liver in palpation (6). We conducted a retrospective study between March 1996 and March 2007 to review medical records of infants with NC. Patients were all admitted in Children’s Hospital Medical Center affiliated to Tehran University of Medical Sciences, which is the major tertiary pediatric referral center in Iran. We reviewed medical records of 250 infants with NC. Infants were excluded if they did not have liver biopsy results, definite diagnosis or complete data on their medical records. Ultimately, 88 infants with BA confirmed by exploratory laparotomy or INH confirmed by liver biopsy were enrolled into the study. In this study, the gold standard tests were liver biopsy and exploratory laparotomy in INH and BA cases, respectively. The sensitivity, specificity and predictive values of HIDA scan and Alagille criteria were evaluated in comparison with liver biopsy and surgical findings. Chi-square test was used for comparison and P < 0.05 was taken as significant. There were 88 infants with NC, including 49 (55.7%) boys and 39 (44.3%) girls. Of these, 63 (37 boys, 26 girls) were diagnosed to have INH and the remaining 25 (12 boys, 13 girls) had BA, according to liver biopsy (P = 0.361). Laparotomy confirmed liver biopsy results in all 25 cases of BA. It means that liver biopsy had 100% accuracy in diagnosing BA. Thirty-three patients had HIDA scan. Among the 23 cases with a positive scan for BA (Figure 1), 14 of them also had BA in liver biopsy (P = 0.031). Among 15 patients with a positive liver biopsy for INH, HIDA scan had shown INH in only two cases (P = 0.15). Figure 1. HIDA scan report of a patient with biliary atresia Among 18 cases who had all four criteria of Alagille accommodated with INH, 14 (77.8%) cases had INH in liver biopsy (P = 0.0514). Of the five patients who had all four Alagille criteria accommodated with BA, in two (40%) cases, liver biopsy showed BA (P = 0.554). So the accuracy of Alagille criteria in our study is lower than what is reported in the pediatric GI textbooks. HIDA scan had a diagnostic accuracy of 60% and 11% for BA and INH, respectively. In conclusion, there is not a single imaging test or clinical feature that has sufficient sensitivity and specificity to differentiate BA from INH, but according to our study hepatobiliary scintigraphy had a good sensitivity for diagnosing BA and the presence of acholic stools and hepatomegaly is significantly higher in infants with BA. So, scintigraphy and clinical features can help in the assessment of any infant with NC to arrive at a timely diagnosis for appropriate management. Since percutaneous liver biopsy is highly accurate in diagnosing BA, in developing countries such our country, using this modality is cost-effective, and it can preclude unnecessary surgical exploration.

Zinc deficiency, which is common in patients with cystic fibrosis (CF), can lead to several complications that may increase the number of hospital admissions in this group of patients. As supplementary zinc can prevent such complications, this study was performed to evaluate the effect of supplementary zinc on body mass index (BMI), forced expiratory volume in one second (FEV1) and number of hospitalizations in CF patients. In this study, 30 children with CF, who were referred to the Digestive Diseases Clinic of the Children's Medical Center in Tehran, were enrolled. Supplementary zinc of 2 mg/kg per day was administered to all patients. Serum level of zinc, alkaline phosphatase, and albumin as well as BMI, FEV1, and number of hospitalizations were compared before and after zinc administration. Height (p0.001), weight (p0.001) and BMI (p=0.001) were significantly increased after zinc, while the number of hospitalizations was significantly decreased (p=0.023). In contrast to patients with normal pulmonary function tests who received supplement therapy, BMI was not increased in those with abnormal pulmonary function after supplementary zinc. Supplementary zinc can increase BMI in CF patients, mostly in those with normal pulmonary function. While supplementary zinc may decrease the number of hospitalizations, other factors can also influence the hospitalization number.

Objective: Celiac disease is an autoimmune disorder in which the risk of autoimmune liver disease is high. Autoimmune hepatitis is a chronic and progressive entity and the risk of its being associated with other autoimmune disorders such as celiac disease is high also. The aim of this study was to determine the prevalence of celiac disease in patients with autoimmune hepatitis and vice versa. Methods: In a cross-sectional study children with autoimmune hepatitis underwent serological screening and endoscopy for celiac disease. In patients with celiac disease, serum aminotransferases were measured and, if abnormal, autoantibodies related to autoimmune hepatitis were checked and needle liver biopsy was performed. Findings: Of the 96 patients, 64 had autoimmune hepatitis and 32 celiac disease. Among patients with autoimmune hepatitis only three (4.7%) were compatible with celiac disease. In the group of patients with celiac disease, autoimmune hepatitis was confirmed in four (12.5%) cases. We consider important to state that 3.1% of this group had celiac hepatitis. Conclusion: Autoimmune liver disease is sometimes associated with latent celiac disease. Serological screening for celiac disease should be routinely done in patients with abnormal serum aminotransferases, particularly those with chronic liver disease. On the other hand, celiac disease is often accompanied by other autoimmune diseases, including autoimmune hepatitis.

Cystic fibrosis (CF) is a common autosomal recessive disorder with different clinical manifestations, mainly in the gastrointestinal and respiratory tracts. This study was performed to access the effect of probiotics in the status of intestinal inflammation in a group of children with CF by measuring the calprotectin level in the fecal samples. Forty-seven patients with CF were enrolled in this study. The fecal calprotectin levels were measured by enzyme linked immunosorbent assay. In a randomized systematic method, the children were divided into two groups - one group received probiotic powder and another received placebo for four weeks. After this period, fecal calprotectin was re-measured. Thirty-one of 47 enrolled patients (65.9%) had abnormal fecal calprotectin levels (50 g/g). After the intervention, the fecal calprotectin levels decreased in 29 patients (21 patients in the drug group, and only 8 patients in the placebo group; p0.001). This study showed that about two-thirds of patients with CF had intestinal inflammation based on fecal calprotectin levels. Probiotic administration was shown to decrease calprotectin concentrations and subsequently intestinal inflammation in CF patients.

Ulcerative colitis (UC) is a form of inflammatory bowel disease, which occasionally can be associated with autoimmune disorders. Herein, a two-year-old male infant with UC under sulfasalazine therapy is presented, who consequently developed type I diabetes mellitus, autoimmune hepatitis and autoimmune hypothyroidism. Although presence of concurrent autoimmune diseases with UC is a rare condition, it could highlight the role of immune-related mechanisms as a pathogenesis of disease.

Objective A variety of sign, symptoms and laboratory findings are more common in children with organic abdominal pains. This study was performed to evaluate the prevalence of organic and functional abdominal pains and relation of red flags to organic pains in 100 children with recurrent abdominal pain (RAP). Methods One hundred consecutive patients with RAP were enrolled in the study. A complete interview and physical examination was made for each patient, accompanied by a series of laboratory, clinical and para-clinical examinations. The data were recorded and analyzed. Logistic regression analysis was used to model and formulize correlations between sign, symptoms, and laboratory findings with organic and functional abdominal pain. Findings Among 100 patients (52% male, 48% female, Age: 9.29±3.17) diagnostic works up revealed organic pain for 57 patients. The most common symptoms of the patients included constipation, diarrhea, chest pain, cough, headache, vomiting, hematuria, and dysuria. Fecal incontinence, delayed puberty, organomegaly, jaundice, and family history of inflammatory bowel disease were reported in none of the patients with RAP. Fever, pain not located in periumbilical area, nocturnal pain, elevated erythrocyte sedimentation rate, weight loss, growth disorder, and abdominal tenderness were among the red flags which revealed diagnosis of organic pain in this study. Conclusion A series of red flags could increase likelihood of finding organic pain in children with RAP.

Morbus Crohn (MC) ist eine chronisch entzundliche Erkrankung des Verdauungstrakts. Die genaue Atiologie der Erkrankung ist zwar immer noch unbekannt, aber mehrere Studien haben in Assoziation mit MC uber Mutationen im CARD15/NOD2-Gen berichtet. Die vorliegende Studie wurde durchgefuhrt, um herauszufinden, ob das CARD15/NOD2-Gen padiatrische Patienten im Iran zu MC pradisponiert. Alle 12 kodierenden Exons des CARD15/NOD2-Gens wurden bei 16 Crohn-Patienten mit Krankheitsbeginn im Kindesalter sequenziert. Die Sequenzierung des CARD15/NOD2-Gens ergab keine Mutationen. Zwei Patienten hatten jedoch einen Polymorphismus in diesem Gen. Bei einem 10-jahrigen Madchen mit mild verlaufendem MC, das eine rektovaginale und perianale Fistel und multiple Marisken hatte, wurde der heterozygote SNP (Single Nucleotide Polymorphism) rs3135500 C > Y im Exon 12.3 gezeigt. Ein 5-jahriger Junge mit moderatem bis schwerem MC sowie einer Anamnese von perianalen Fissuren und oraler Candidiasis hatte einen heterozygoten SNP in den Exons 4.1 and 12.1. Die Ergebnisse dieser Studie zeigen, dass CARD15/NOD2-Mutationen bei iranischen Patienten mit MC-Beginn im Kindesalter nicht fur die Pathogenese der Erkrankung verantwortlich sind.

Objective Recurrent abdominal pain (RAP) by itself is one of the common reasons in child-aged patients to refer to a clinician. Some of these patients are presented with more serious features, so-called the “red flag”. The most important issue in management of RAP is to distinguish the type of it, whether it is functional or organic. In this study we aimed to assess the redundancy of red-flagged RAP with findings of esophago-gastro-deudonoscopy. Methods In a 2 year prospective study 150 consecutive children with RAP who showed red flags underwent esophago-gastro-deudonoscopy. The prevalence of each finding was recorded. Overall positive predictive value of predicting an endoscopic finding while having a red-flag was calculated. Findings Among all the patients, 126 cases showed at least a positive finding in their endoscopy that corresponded to the positive predictive value of 84% for predicting the presence of an endoscopic finding according to red flags. Interestingly, 20% of patients showed hiatus hernia when surveyed. Conclusion Comprehensive physical examination is needed to avoid performing esophago-gastro-deudonoscopy without indication in patients with recurrent abdominal pain.

Nowadays, there is an increasing interest in noninvasive methods to diagnose Helicobacter pylori infection. Indeed, they can profitably replace endoscopy in predicting the diagnosis. The stool antigen test for H. pylori is a noninvasive immunoassay to diagnose active infection with this bacterium in human fecal samples. The aim of this study was detection of alkyl hydroperoxide reductase protein (AhpC) antigen by immunoblotting in stool samples for diagnosis of H. pylori.Chromosomal DNA from H. pylori was isolated. AhpC gene was amplified by PCR, These amplicons were cloned into pTZ57R/T cloning vector then subcloned into pQE30 expression vector and overexpressed using isopropyl-beta-D-thiogalactopyranoside in E. coli M15. AhpC protein was purified by affinity chromatography. Rabbits were immunized with the purified AhpC protein for the production of antibodies. To determine the accuracy of the test for diagnosing H. pylori infection from stool, we evaluated 84 patients (6-81 years old) using Western blot analysis by rabbit anti-AhpC antibody. Positive rapid urease test on biopsy samples was considered as the gold standard.AhpC gene was overexpressed, and AhpC protein was purified. Rabbit anti-AhpC antibody produced after immunization with the purified AhpC protein. By immunoblotting, we detected AhpC protein in the positive stool samples. The test showed a 83.3% sensitivity (95% CI: 69.8-92.5%) and a 91.7% specificity (95% CI: 77.5-98.2). Among the children, the sensitivity was 88.2% (95% CI: 63.6-98.5) and the specificity was 100% (95% CI: 69.2-100); in adults, the sensitivity and specificity were 80.6% (95% CI: 62.5-92.5) and 88.5% (95% CI: 69.8-97.6), respectively.Using of AhpC antigen for diagnosis of H. pylori infection is a useful noninvasive method, accurate in adolescents and children, and can be used for the development of a stool antigen detection kit for H. pylori.

Abetalipoproteinemia (ABL), or Bassen-Kornzweig syndrome, is a rare autosomal recessive disorder of lipoprotein metabolism, characterized by fat malabsorption, hypocholesterolemia retinitis pigmentosa, progressive neuropathy and acanthocytosis from early infancy. We describe the clinical and molecular characterization of a 6-month-old infant born of consanguineous, apparently healthy parents from Iran. The patient was hospitalized because of failure to thrive, greasy stool and vomiting. The patient's serum lipid profile, the clinical phenotype and the duodenal histology suggested the clinical diagnosis of ABL. The MTP gene analysis by direct sequencing revealed a novel homozygous mutation (c.1586 A > G-H529R). The parents were heterozygotes for the same mutation and interestingly the father showed a lipid profile characterized by a slight reduction of total and LDL-cholesterol plasma levels.

Objective Wilson's disease (WD) is an autosomal recessive disease with genetic abnormality on chromosome 13 causing defect in copper metabolism and increased copper concentration in liver, central nervous system and other organs, which causes different clinical manifestations. The aim of this study was to determine the sensitivity of different clinical and paraclinical tests for diagnosis of Wilson's disease. Methods Paraffin blocks of liver biopsy from 41 children suspicious of WD were collected. Hepatic copper concentrations were examined with atomic absorption spectrophotometry (Australian GBC, model: PAL 3000). Fifteen specimens had hepatic copper concentration (dry weight) more than 250μg/g. Clinical and laboratory data and histologic slides of liver biopsies of these 15 children were reviewed retrospectively. Liver tissue was examined for staging and grading of hepatic involvement and also stained with rubeonic acid method for copper. Findings Patients were 5-15 years old (mean age=9.3 years, standard deviation=2.6) with slight male predominance (9/15=60%). Five (33%) patients were 10 years old. Three (20%) of them were referred for icterus, 8 (54%) because of positive family history, 2 (13%) due to abdominal pain and 2 (13%) because of hepatosplenomegaly and ascites. Serum AST and ALT levels were elevated at the time of presentation in all patients. In liver biopsy, histological grade and stage was 0-8 and 0-6 respectively, 2 (13%) had cirrhosis, 1 (7%) had normal biopsy and 12 (80%) showed chronic hepatitis. Hepatic copper concentrations were between 250 and 1595 μg/g dry weight. The sensitivity of various tests were 85% for serum copper, 83% for serum ceruloplasmin, 53% for urinary copper excretion, 44% for presence of KF ring and 40% for rubeonic acid staining on liver biopsies. Conclusion None of the tests stated in the article were highly sensitive for diagnosis of WD, so we suggest that diagnosis should be based on combination of family history, physical examination and different tests.

Background/Aims Gastroesophageal reflux disease (GERD) and cow's milk allergy (CMA) are two common conditions that occur in infancy. This study was performed to investigate the frequency of CMA in a group of patients with GERD. Methods Eighty-one children with signs and symptoms of GERD were enrolled in this study. All subjects received omeprazole for 4 weeks after the initial evaluation. Empirical elimination of cow's milk from the diet was started for the patients who did not respond to the omeprazole treatment. Results Seventy-two cases presented with gastrointestinal signs and symptoms, whereas the remaining nine cases presented with respiratory complaints. After the initial treatment with omeprazole, two thirds of the cases (54 patients, 66.7%) responded well, and all of their symptoms were resolved. Cow's milk was eliminated from the diets of the remaining 27 patients. All signs and symptoms of GERD were resolved in this group after a 4 week elimination of cow's milk from the diet. Conclusions A diagnosis of CMA was considered in one third of the pediatric cases with signs and symptoms of GERD. This finding shows that CMA can mimic or aggravate all signs and symptoms of severe GERD during infancy.

Crohn's disease (CD) and ulcerative colitis (UC) are two inflammatory bowel diseases (IBD) characterized by chronic intestinal inflammation. In this study, the clinical characteristics of a cohort of pediatric patients with IBD are reviewed and their responses to induction therapy are evaluated. The severity of disease for 43 patients (20 with CD and 23 with UC) was determined using the PCDAI and PUCAI and based on the initial severity, before treatment was started. Following treatment, the severity of disease was re-evaluated at 6 months after the initial diagnosis. The patients in both groups had mild-to-severe disease. The mean PCDAI and PUCAI values were 60.62 +/- 16.48 and 50.95 +/- 9.35, for CD and UC patients, respectively. Most patients (83.7 %) responded to standard treatments with a significant reduction in the PCDAI and PUCAI scores from baseline (p value < 0.001). At the primary endpoint of 24 weeks, 54 % of all patients were in clinical remission; 16 of 23 in the UC group (70 %) and 6 of 20 in the CD group (30 %). The results of this study provide evidence that subgrouping pediatric patients with IBD into distinct clinical phenotypes based on severity of the initial presentation may provide better means of management of this group. This approach can result in a better response to treatment and reduce the side effects of unnecessary therapy.

Cystic fibrosis (CF) is a hereditary disease, characterized by chronic pulmonary disease, pancreatic insufficiency and abnormal electrolytes in the sweat. In order to evaluate the clinical manifestations and laboratory findings of Iranian children with CF during a 10-year period, 243 CF patients, with a median age of 5 months, were investigated in this study. The most common manifestations were gastrointestinal disorders and respiratory manifestations. Cough was the most common symptom, followed by malnutrition, diarrhea, respiratory distress, and vomiting. The frequency of these findings after treatment was significantly decreased in comparison with the period before diagnosis. During the mean follow-up of 40.9 months, seven cases died due to severe infections. Cystic fibrosis as a common genetic disorder should be considered in any child with recurrent gastrointestinal and respiratory manifestations, since delayed diagnosis could lead to severe complications and even death in this group of patients.

Aim of Study: Chronic gastritis is defined as the presence of chronic mucosal inflammatory changes leading eventually to mucosal atrophy and epithelial metaplasia. This condition constitutes a background for dysplasia and thereby carcinoma. Detection of exact histopathology of inflammatory process is necessary in biopsy specimen. We designed the current study to determine the value of taking more sections in small gastric biopsies for better histopathologic evaluation. Materials and Methods: Gastric biopsy specimen of children who suffered from gastrointestinal (GI) symptoms was sent in 10% formalin to our laboratory. After routine processing, three slides with several sections on them were taken from the specimen: t0 he first was named the superficial section, the second was stained by Giemsa and the third was named deep section (further sections after this slide will diminish in size). The slides were not taken exactly consecutively but several sections were discarded between them. The purpose of this study is to compare the superficial and deep sections for detection of inflammatory processes. Results: In 1062 specimens the results of superficial section and deep section were the same (87.1%) and in 158 specimens the results were different. In 88 (7.2%) specimens deep section was diagnostic. The difference was seen usually as normal tissue in superficial sections but presence of lymphoid follicle in deep sections. The difference between superficial and deep sections was statistically significant. Although obtaining more sections will put an economic burden on the laboratory, we propose that in small gastric biopsies, it is helpful in better evaluation of histopathological changes.

Inflammatory bowel disease (IBD) is a group of disorders, including Crohn's disease (CD), ulcerative colitis (UC) and indeterminate colitis (IC). Small intestine and colon are primarily affected in this group of disorders.This single center study was performed to define demographic features and clinical characteristics of Iranian pediatric patients with IBD.Fifty nine patients with IBD, who have been referred to Children's Medical Center Hospital during a 10-year period, were investigated in this study. The data was gathered by interviewing the patients and their families, as well as reviewing their medical records.Among 59 patients with IBD, 23 cases had UC and 19 cases had CD, while the remaining 17 cases had IC. Patients with UC were significantly younger at the time of diagnosis in comparison with patients with CD. The most common symptoms were abdominal pain, diarrhea, fever and growth failure. Hepatobiliary abnormalities and arthritis were common extra intestinal manifestations. The median Pediatric Crohn's Disease Activity Index was 42.5 (range 20-60), whereas the median Pediatric Ulcerative Colitis Activity Index was 40 (range 20-70). Seven of 23 UC (30.4%) had proctatis, while 16 (69.6%) had extensive colitis. In CD, 11 of 19 (57.9%) had involvement of terminal ileum and colon, while inflammation was limited to the colon in 8 cases (42.1%). The colonoscopic findings in the IC group were heterogeneous.This study provides epidemiological data on pediatric patients with IBD, which could be useful for health care workers in prompt diagnosis and appropriate treatment of early onset IBD.

Objective Hepatitis C virus (HCV) is an etiological agent responsible for occurrence of post-transfusion hepatitis in thalassemic patients. This study identified hepatitis C genotypes in pediatric and adolescent thalassemic patients and their correlation with age, blood transfusion, HCV RNA viral titer and liver function. Methods This study considers cross-sectional data from the Center for Thalassemia in Zahedan (Iran) carried out between August 2005 and September 2007. Twenty multitransfused patients suffering from β-thalassemia major and chronic HCV infection (13 males, 7 females) were included in the study. Patients were considered eligible for the study if they were seropositive for HCV RNA polymerase chain reaction (PCR) before initiation of evaluation. Blood sample was taken for HCV genotype and viral titer as well as biochemical markers. Type specific primer and real-time RT-PCR HCV were used for determination of viral genotype and HCV-RNA titer. Findings There was a significant positive correlation between serum HCV RNA titer and genotypes (P

Objective Reinfection rate of Helicobacter pylori after successful eradication is low in developed countries. This study was performed to determine the reinfection rate of H. pylori during a follow up period of 12 months in Iranian children. Methods In this prospective study, children with H. pylori infection were treated with triple omeprazole based regimen. Patients with negative 13C urea breath test (UBT) performed after 8 weeks of therapy, were followed up by the same test after 1 year. Findings Thirty seven patients, aged 5 to 17 years, were studied. Among them 25 (67.5%) were boys. After eradication therapy of H. pylori, 34 patients had negative 13C UBT. Reinfection occurred in 5 (14.7%) patients. Reappearance or continuing symptoms after treatment were associated with higher rate of recurrence (P=0.042). Conclusion Recurrence rate of H. pylori was high in our children. Successful eradication significantly decreased complaints and further symptoms. Follow up and reevaluation of patients is necessary especially when there are symptoms after eradication.

Object Previous studies have shown nutritional benefits of breastfeeding for a child's health, especially for protection against infection. Protective factors in human milk locally and systemically prevent infections in the gastrointestinal as well as upper and lower respiratory tracts. It remains unclear whether breastfeeding protects infants against ventriculoperitoneal (VP) shunt infection. Methods A cohort study was conducted from December 2003 to December 2006 at Children's Hospital Medical Center in Tehran, Iran. A total of 127 infants with hydrocephalus who were treated using a VP shunt in the first 6 months of life were enrolled. Each infant's breastfeeding method was classified as either exclusively breastfed (EBF), combination feedings of breast milk and formula (CFBF), or exclusively formula-fed (EFF). Infants were followed up to determine the occurrence of shunt infection within 6 months after operation. Statistical analysis was performed using survival methods. Results Infants ranged in age from 4 to 170 days at the time of shunt insertion (mean 69.6 days), and 57% were males. Regarding the breastfeeding categories, 57.5% were EBF, 25.2% were CFBF, and 17.3% were EFF. During the follow-up, shunt infection occurred in 16 patients, within 15 to 173 days after shunt surgery (median 49 days). The 6-month risk of shunt infection was 8.5% (95% confidence interval [CI] 4–18%) in the EBF group, 16.5% (95% CI 7–35%) in the CFBF group, and 26.0% (95% CI 12–52%) in the EFF group. There was no statistically significant difference between these 3 groups (p = 0.11). The trend test showed a significant trend between the extent of breastfeeding and the risk of shunt infection (p = 0.035), which persisted even after adjustment for potential confounding variables (hazard ratio = 2.01, 95% CI 1.01–4). Conclusions This study supports the protective effect of breastfeeding against shunt infection during the first 6 months of life and the presence of a dose–response relationship, such that the higher the proportion of an infant's feeding that comes from human milk, the lower the incidence of shunt infection. Encouraging mothers of infants with VP shunts to breastfeed exclusively in the first 6 months of life is recommended.

Introduction Several conditions are considered in differential diagnosis of neonatal cholestasis. Of these the most important is extrahepatic biliary atresia (EHBA), while prompt diagnosis and surgical correction of obstruction can ameliorate clinical symptoms, provides long term survival for about one fourth of patients and serves as an important bridge to transplantation for many others. From histopathologic standpoint, features of EHBA overlaps with other diagnoses and so ancillary tests such as immunohistochemical staining for CD56 is suggested by some authors as a helpful tool in differential diagnosis. Hereby we wanted to examine this staining in our center which is a referral children hospital and to prove its efficacy in our problematic cases. Materials and Methods By retrospective review of pathology records during 2000 to 2006 in Markaze Tebbi Koodakan (children hospital related to Tehran University of Medical Sciences), we selected 17 cases of EHBA as patients and 12 cases with other diagnoses as controls, both with some degree of bile ductular proliferation in liver biopsies. EHBA cases were all proved by surgery. Four of control cases also underwent surgery but proved to have open ducts by intra-operative cholangiography. Long term follow up and other tests ruled out EHBA in other 8 cases. Hematoxylin-Eosin stains of paraffin blocks were studied again and freshly prepared sections were immunostained for CD56. Results Bile ducts and proliferating bile ductules were strongly positive for CD56 in 6 of 17 cases of EHBA. In 7 out of 17, positivity were seen in more than two thirds of portal tracts. In controls, one case showed strong positivity and 6 out of twelve showed positivity in more than two thirds of portal tracts. The intensity and distribution of CD56 staining did not differ significantly between two groups. Discussion Despite findings of previous studies, we have shown that CD56 staining can not help as an ancillary test in differential diagnosis of neonatal cholestasis and perhaps other markers should be tested in this regard.

We evaluated two protocols for isolation of Helicobacter pylori in stool from biopsied and nonbiopsied children. Twenty-three child patients whose presumptive positivity or negativity was diagnosed by endoscopy and a rapid urease test at site were used to compare biopsy-based tests with stool-based tests (H. pylori stool antigen test and stool culture). Their gastric activity and bacterial density were graded by the updated Sydney system. Biopsy and stool specimens were cultured on Campy-blood and Belo horizonte agar plates after enrichment in selective Campy-Thio medium. To compare two stool culture protocols, stools from 20 nonbiopsied children were tested by the HpSA test and cultured either as above or after treatment with cholestyramine. Grown colonies were screened by Gram staining, slide agglutination using anti-H. pylori monoclonal IgG; positive isolates were tested by biochemical tests and polymerase chain reaction for H. pylori-specific ureA gene. Coccoid H. pylori was isolated in stool samples from the biopsied patients whose bacterial density was two to four in histology. Their oxidase was slightly positive but became positive after two subcultures, while additional biochemical tests confirmed the isolation of H. pylori. Similar coccoid but oxidase positive H. pylori was isolated from three nonbiopsied children with the protocol of cholestyramine treatment only. The density of bacteria in the stomach may influence the recovery of H. pylori from stool; inactivation of bile with cholestyramine improves the yield in culture and favors isolation of an enhanced metabolic form of bacteria.

Antibiotic susceptibility testing of 70 pediatric Helicobacter pylori isolates was performed by using screening agar and disk diffusion methods. Resistance to metronidazole and tinidazole was 72 to 79% and 71 to 81% by modified disk diffusion and 77% and 78% by screening agar, respectively. Susceptibilities to amoxicillin, ampicillin, clarithromycin, tetracycline, erythromycin, and ciprofloxacin were 58, 69, 75, 68, 68, and 65%, respectively.

Aim To evaluate the usefulness of stool-PCR test for diagnosis of Helicobacter pylori (H pylori) infection in pediatric populations. Methods Based on endoscopic features (including nodular gastritis, erosive duodenitis and ulcer) and/or a positive rapid urease test (RUT) obtained during endoscopy, 28 children from a group of children admitted to the Children's Medical Center of Tehran for persistent upper gastrointestinal problems were selected to compare biopsy-based tests with stool-PCR. Their gastric activity and bacterial density were graded by the updated Sydney system, and their first stool after endoscopy was stored at -70 degrees C. Biopsies were cultured on modified campy-blood agar plates and identified by gram-staining, biochemical tests, and PCR. Two methods of phenol-chloroform and boiling were used for DNA extraction from H pylori isolates. Isolation of DNA from stool was performed using a stool DNA extraction kit (Bioneer Inc, Korea). PCR was performed using primers for detection of vacA, cagA, and 16srRNA genes in both isolates and stool. Results Sixteen out of 28 child patients (57%) were classified as H pylori positive by biopsy-based tests, of which 11 (39%) were also positive by stool-PCR. Sensitivity and specificity of stool-PCR was 62.5% and 92.3% respectively. H pylori was observed in histological sections for 10 out of 11 stool-positive patients. Association was observed between higher score of H pylori in histology and positivity of stool-PCR. Also association was observed between the more severe form of gastritis and a positive stool-PCR. Conclusion Association between higher score of H pylori in histology and a positive stool-PCR make it a very useful test for detection of H pylori active infection in children. We also suggest that a simple stool-PCR method can be a useful test for detection of H pylori virulence genes in stool.

Introduction Extra-hepatic biliary atresia (EHBA) is an important cause of neonatal cholestasis. Several infectious agents have been proposed as etiologic factors such as Rotavirus and Reovirus. There is limited data on the role of Epstein Barr virus (EBV) infection in EHBA, so we decided to study the presence of EBV virus in a series of 16 proven EHBA cases by Chromogenic in situ hybridization (CISH) technique. Methods In the current study a total of 16 liver wedge biopsies of proven cases of EHBA were selected in a period of 4 years. CISH staining for EBV-encoded RNA (EBER) transcript was performed. Results The review of H&E-stained slides of liver biopsies revealed fibrosis and marked ductular proliferation. In CISH-stained slides, EBV trace was observed in hepatocytes in two cases and in biliary epithelium in one case of EHBA. Discussion Considering the association of hepatitis with the Epstein-Barr virus in later life, it is likely that EBV hepatitis and its complications occur in the neonatal/perinatal period. Since EHBA is a relatively rare disease, a similar study on wedge biopsies of this number of proven cases of EHBA has not been performed to date. Current observation proposes the need for a study of larger series and employing other methods for confirming the etiologic role of EBV in EHBA cases.